Changes in hippocampal NMDA-R subunit composition induced by exposure of neonatal rats to L-glutamate.
Overactivation of NMDA-Rs may mediate excitotoxic cell death associated with epileptic seizures, and hypoxic-ischemic conditions. We assessed whether repeated subcutaneous administration of l-glutamate to neonatal rats affects the subunit composition of NMDA-Rs. Accordingly, cortical and hippocampal tissue from 14-day-old rats was analyzed by Western blotting and RT-PCR to quantify the protein and mRNA expression of different NMDA-R subunits. In addition, tissue sections were Nissl stained to assess the cell damage in this tissue. Early exposure of neonatal rats to L-glutamate differentially affects the expression of mRNA transcripts for NMDA-R subunits in the cerebral cortex and hippocampus. In the cerebral cortex, a decrease in NR2B subunit mRNA expression was observed, as well as a loss of NR1 and NR2A protein. By contrast, neonatal L-glutamate administration augmented the transcripts encoding the NR1, NR2B, and NR2C subunits in the hippocampal formation. The expression of mRNA encoding the NR2A subunit was not affected by neonatal L-glutamate administration in either of the brain regions examined. This differential expression of NMDA-R subunits following neonatal exposure to L-glutamate may represent an adaptive response of the glutamate receptors to overactivation in order to reduce the effect of high L-glutamate during the early period of life when the animal is more vulnerable to excitotoxicity.
Rivera-Cervantes
M C
MC
Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias (CUCBA), Universidad de Guadalajara, Guadalajara, Mexico.
Flores-Soto
M E
ME
Chaparro-Huerta
V
V
Reyes-Gómez
J
J
Feria-Velasco
A
A
Schliebs
R
R
Beas-Zárate
C
C
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009498:Neurotoxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; C432823:NR2C NMDA receptor; C464436:NR2D NMDA receptor; D009498:Neurotoxins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid